The ability to detect and procure food is an important survival mechanism; however, in the modern environment where food is readily available and easily obtained, this once important survival mechanism may now be a contributing factor to the obesity epidemic. Animals use cues associated with food stimuli to determine where to obtain food, and to identify which foods are safe to eat, most nutritionally valuable and most rewarding. Cues that predict food activate the brain reward system to stimulate food seeking behavior; importantly cues alone can stimulate food intake in sated animals. Therefore cue-induced feeding has been hypothesized to cause excessive food intake culminating in obesity [Castellanos et al., 2009; Nijs et al., 2010]. Food cues activate specific nuclei within the mesolimbic dopamine and opioid systems, and there is a significant overlap in activation within these areas with that produced by drugs of abuse [Avena et al., 2008; Kelley et al., 2000; Rada et al., 2005; Spangler et al., 2004]. Recent findings from our laboratory and others have implicated lateral orexin neurons in preference for cues associated with food and drug reward as well as in reward-seeking behaviors, including cue-induced reinstatement to extinguished food-seeking and drug- seeking [Borgland et al., 2009; Cason et al., 2010; Cason and Aston-Jones, 2013a; Cason and Aston-Jones, 2013b; Choi et al., 2010; Choi et al., 2012; Harris et al., 2005; Smith et al., 2009; Smith and Aston-Jones, 2012]. The studies outlined in this proposal will use a combination of optogenetic and pharmacological techniques to investigate the specific orexin circuitry that mediates conditioned responding to sweets during cue-elicited saccharin-seeking.